Traumatic brain injury (TBI) is an important cause of death in young adults and children. Till now, the treatment of TBI in the short- and long-term complications is still a challenge. Our previous evidence implied
aquaporin 4 (AQP4) and
hypoxia inducible factor-1α (HIF-1α) might be potential targets for TBI. In this study, we explored the roles of AQP4 and HIF-1α on
brain edema formation, neuronal damage and neurological functional deficits after TBI using the controlled cortical injury (CCI) model. The adult male Sprague Dawley rats were randomly divided into
sham and TBI group, the latter group was further divided into neutralized-AQP4 antibody group,
2-methoxyestradiol (2-ME2) group, and their corresponding control,
IgG and isotonic saline groups, respectively.
Brain edema was examined by water content. Hippocampal neuronal injury was assessed by neuron loss and neuronal skeleton related
protein expressions. Spatial learning and
memory deficits were evaluated by Morris water maze test and memory-related
proteins were detected by western blot. Our data showed that increased
AQP4 protein level was closely correlated with severity of
brain edema after TBI. Compared with that in the control group, both blockage of AQP4 with neutralized-AQP4 antibody and inhibition of HIF-1α with 2-ME2 for one-time treatment within 30-60 min post TBI significantly ameliorated
brain edema on the 1st day post-TBI, and markedly alleviated hippocampal neuron loss and spatial learning and
memory deficits on the 21st day post-TBI. In summary, our preliminary study revealed the short-term and long-term benefits of targeting HIF-1α-AQP4 axis after TBI, which may provide new clues for the selection of potential therapeutic targets for TBI in clinical practice.